1. Field of the Invention
Embodiments of the invention relate generally to formulations comprising dimethyl sulfoxide (DMSO) alone or in combination with methylsulfonylmethane (MSM) to treat infectious diseases. Certain embodiments relate to sensitizing drug-resistant microbes to drugs. Several formulations disclosed herein are useful for treating drug-resistant tuberculosis.
2. Description of the Related Art
Infectious diseases are diseases caused by pathogenic microbial agents, including viruses, bacteria, fungi, parasites, and prions, among others. The pathogenic agents may be primary or opportunistic pathogens. Primary pathogens cause infection as a direct result of their virulence, while opportunistic pathogens typically require a compromised host defense system to produce an infection. Examples of common infectious diseases include HIV/AIDS, measles, tetanus, tuberculosis, malaria, upper and lower respiratory infections, and hepatitis. While modern medicine has reduced the prevalence of many infectious diseases, particularly in developed countries, they still account for a large degree of morbidity and mortality.
Tuberculosis, malaria, HIV/AIDS, and diarrhoeal diseases are the leading killers among the infectious diseases. Tuberculosis (tubercle bacillus) is caused by mycobacteria, primarily Mycobacterium tuberculosis. Tuberculosis primarily infiltrates the lungs (pulmonary tuberculosis), but has also been documented as affecting the central nervous system, the lymphatic system, and the circulatory system, among others. Other mycobacteria may also cause tuberculosis, for example, Mycobacterium bovis, Mycobacterium africanum, Mycobacterium canetti, and Mycobacterium microti. However, these species are less common in humans.
Despite certain improvements in medical treatment for infectious diseases (antibiotics and vaccines), there remain many obstacles to reducing the mortality caused by these diseases. A primary issue is the emergence and spread of drug resistant pathogens. Tuberculosis and other infectious diseases have shown resistance to first-line drugs. In some instances, resistance has progressed to require a change to more expensive second or third-line agents. Evolution of pathogenic microorganisms is expected due to the selective pressure of drug therapy. However, resistance is exacerbated by several factors, including abuse, underuse or misuse of antimicrobials, poor patient compliance, and poor quality of available drugs.
Dimethyl sulfoxide (DMSO; (CH3)2(SO)) is a polar, aprotic solvent widely used as a solvent. It is frequently used in various chemical and biological reactions and as a cryoprotectant for cell storage. The strong unpleasant odor of DMSO (or metabolites), among other side effects, has adversely impacted the use of DMSO in medical applications.
Methylsulfonylmethane (MSM; (CH3)2SO2)), also known as dimethyl sulfone, is an organosulfur compound that is a metabolite of DMSO and certain sulfur-containing amino acids. MSM has been marketed primarily as a dietary supplement.